Melatonin reduces torsion–detorsion injury in rat ovary: biochemical and histopathologic evaluation Introduction Ovarian torsion is a serious gynecologic problem where conservative management includes detorsion of the in- volved segments [1–4]. Torsion has been implicated in ovarian damage and infertility, and detorsion is one of the most important factors in further injury. Ovarian injury resulting from torsion/detorsion resembles that caused by ischemia/reperfusion (I/R) injury observed in other organs. Reactive oxygen species (ROS) such as superoxide free radical (O  2 ), hydrogen peroxide (H 2 O 2 ), and hydroxyl free radical ( • OH) have been implicated in the pathogenesis of tissue injury during I/R [5]. These reactive species are formed continuously in cells as a consequence of both oxidative biochemical reactions and external factors. The ROS interact with lipids, proteins and nucleic acids, resulting in loss of membrane integrity, and structural or functional changes in proteins [5–7]. Melatonin is a biologically relevant indole compound. Melatonin is a free radical scavenger antioxidant which protects cells against the damage induced by several oxidative agents [8, 9]. Although many reports have demonstrated the protective effects of melatonin in various models of I/R injury [10–13], its effect in ovarian I/R injury has not yet been investigated. To determine whether treatment with melatonin modifies the levels of the endogenous indices of oxidative stress, we examined its effects on an in vivo model of adnexial I/R injury in rats. The aim of the present study was to investigate the effects of melatonin on some biochemical parameters including reduced glutathione (GSH), malondialdehyde (MDA) (an index of lipid peroxidation), xanthine oxidase Abstract: This experimental study was designed to determine the effects of melatonin on the levels of malondialdehyde (MDA), reduced glutathione (GSH), xanthine oxidase (XO) after adnexial torsion/detorsion (ischemia/ reperfusion, I/R) of the ovaries of in rats. Forty adult albino rats were divided into five groups: sham operation, torsion, I/R plus saline, I/R plus melatonin and torsion plus melatonin. Rats in the sham-operated group underwent a surgical procedure similar to the other groups but the adnexa was not occluded. Rats in the torsion group were killed after adnexal torsion for 3 hr. Melatonin and saline were injected intraperitoneally (10 mg/kg) 30 min before detorsion to the I/R plus melatonin group and I/R plus saline group respectively. After 3 hr of ovarian detorsion, the rats were killed and ovaries were removed. Melatonin was injected intraperitoneally (10 mg/kg) 30 min before torsion to the torsion plus melatonin group. After 3 hr of ovarian torsion, the rats were killed and ovaries were harvested. The tissue levels of MDA, GSH and XO were measured. MDA and XO levels in the I/R plus saline group increased significantly when compared with torsion and sham-operated groups (P < 0.001). MDA and XO levels in the I/R plus melatonin group were lower than I/R plus saline and differences between the two groups were statistically significant (P < 0.001). GSH levels in the I/R plus saline group decreased significantly when compared with ischemia and sham-operated groups (P < 0.001). GSH levels in the I/R plus melatonin treated rats were significantly higher than I/R plus saline and ischemia groups (P < 0.001). The tissue levels of XO, MDA and GSH were similar between ischemia and ischemia plus melatonin groups. Morphologically, polymorphonuclear neutrophil infiltration and vascular dilatation were obvious in the I/R-damaged ovaries, and the changes also partially reversed by melatonin. This study demonstrates that melatonin protects the ovaries against oxidative damage associated with reperfusion following an ischemic insult. Yusuf Turkoz 1 , Onder Celik 2 , Seyma Hascalik 2 ,Yılmaz Cigremis 3 , Mehmet Hascalik 4 , Bulent Mizrak 5 and Saim Yologlu 6 Departments of 1 Biochemistry and 2 Obstetrics and Gynecology, Inonu University, School of Medicine, Malatya; 3 Department of Biology, Inonu University, Science and Art Faculty, Malatya; Departments of 4 Anaesthesiology, 5 Pathology and 6 Biostatistics, Inonu University, School of Medicine, Malatya, Turkey Key words: malondialdehyde, melatonin, ovarian torsion/detorsion, rat, reduced glutathione, xanthine oxidase Address reprint requests to Yusuf Turkoz, Inonu University, Turgut Ozal Medical Center, Biochemistry Lab. 44315, Malatya, Turkey. E-mail: yturkoz@inonu.edu.tr Received February 6, 2004; accepted April 27, 2004. J. Pineal Res. 2004; 37:137–141 Doi:10.1111/j.1600-079X.2004.00146.x Copyright Ó Blackwell Munksgaard, 2004 Journal of Pineal Research 137